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Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Wilson's disease is a disorder of biliary copper excretion that may result in severe neurological symptoms and advanced liver disease. The wide variation of phenotypic disease expression cannot be fully explained by the different mutations of the Wilson disease gene. In neurological disorders, such as Alzheimer's disease, temporal lobe epilepsy and cerebral trauma, the presence of the apolipoprotein E (ApoE) allele epsilon4 is associated with an increased vulnerability of the brain to the effects of the disease, whereas the presence of the ApoE genotype epsilon3/3 appears to provide moderate neuroprotection. We examined whether this hypothesis holds true for the development of neurological symptoms in patients with Wilson's disease. The ApoE genotype and the H1069Q mutation (the most common in Wilson's disease) status were determined by polymerase chain reaction-based mutation assays in 121 well-characterized, symptomatic index patients with Wilson's disease. An investigation profile was established in which the patients were grouped according to the clinical symptoms at presentation, the ApoE genotypes and the status of the H1069Q mutation. Fifty-nine per cent of the 121 patients had the allele combination ApoE epsilon3/3 (21% ApoE epsilon3/4, 19% ApoE epsilon3/2, 1% ApoE epsilon4/2). The distribution of ApoE genotypes did not deviate from known distributions in healthy European subjects. Within the group of 40 H1069Q-homozygous patients, the onset of symptoms was significantly delayed in patients with the ApoE epsilon3/3 genotype (25 +/- 6 years at presentation) compared with patients with the ApoE epsilon3/4 genotype (20 +/- 3 years at presentation). In this study, the ApoE genotype was established as an important factor delaying the onset of neurological and hepatic symptoms, but not modifying phenotypic disease expression in a homogeneous group of patients with Wilson's disease (all H1069Q-homozygotes, similar genetic background). The presence of ApoE epsilon3/3 attenuates clinical manifestations in Wilson's disease by mechanisms which might involve the antioxidant and membrane-stabilizing properties of the ApoE 3 protein.

We assessed serial event-related potentials (ERPs) as well as neuropsychological and clinical test findings in a group of multiple sclerosis (MS) patients (n = 14) treated with interferon beta-1b (INF-beta-1b) compared to normal controls (n = 14). All investigations were done within 1 week before INF-beta-1b therapy was started and 12 months later. An auditory oddball paradigm was employed. No significant differences in the N100, P200, N200 or P300 latencies between patients and control group were found, but 3 out of 14 MS patients developed abnormal P300 latencies (more than 2 standard errors from the mean) after 1 year of INF-beta-1b therapy. This was not reflected by the respective neurological impairment as assessed by the Expanded Disability Status Scale score. ERPs might be a useful tool in clinical studies in order to evaluate drug effects on cognition, but for a final statement, the analysis of ERPs in a larger group of patients is required., (Copyright 2000 S. Karger AG, Basel)

Immediate diagnostic clarification is required in patients who develop acute or subacute symptoms suggestive of an intraspinal lesion. In case of symptoms indicating a monoradicular lesion a spinal CT investigation is mostly sufficient. Since polyradicular syndromes are often due to inflammation, examination of the cerebrospinal fluid is the most important diagnostic measure. However, in case of symptoms suggestive of intramedullary lesions, spinal MRT is by far the most effective diagnostic procedure. In patients with symptoms suggestive of a lesion of the cauda equina spinal CT is sufficient in most cases as a first measure, particularly if the lesion can be precisely localized by clinical examination. The decision as to which diagnostic method should be performed first is relevant mainly because of the limited availability of MRT examinations within the daily clinical routine. MRT should thus be used selectively in patients with lesions that cannot be identified by alternative diagnostic methods.

Coronal brain slices allow the study of neurotoxicity and "neuroprotection" under conditions where the differentiation-state and interrelationships of the neurones and glial cells are closer to those occurring in the intact tissue than is the case for co-cultured cell systems. The involvement of glial cells in the excitotoxicity of kainate and the potentiation of this toxicity by inhibition of glutamine synthase can be demonstrated. Longer-term toxicity of kainate may also be compounded by depletion of glutathione levels resulting from inhibition of gamma-glutamylcysteine synthase. The involvement of nitric oxide formation in the toxicity of N-methyl-D-aspartate can also be shown. The neurotoxicity of 1-methyl-4-phenylpyridinium can be readily demonstrated in coronal slice preparations. Taurine affords protection against this neurotoxicity. The possible mechanisms of these effects are considered in terms of the cyclic interrelationships between the different events which can lead to cell death.

Purpose: To compare T2-weighted conventional spin-echo (CSE), fast spin-echo (FSE), shorttau inversion recovery (STIR) FSE, and fluid-attenuated inversion recovery (FLAIR) FSE sequences in the assessment of cervical multiple sclerosis plaques., Methods: Twenty patients with clinically confirmed multiple sclerosis and signs of cervical cord involvement were examined on a 1.5-T MR system. Sagittal images of T2-weighted and proton density-weighted CSE sequences, T2-weighted FSE sequences with two different sets of sequence parameters, STIR-FSE sequences, and FLAIR-FSE sequences were compared by two independent observers. In addition, contrast-to-noise measurements were obtained., Results: Spinal multiple sclerosis plaques were seen best on STIR-FSE images, which yielded the highest lesion contrast. Among the T2-weighted sequences, the FSE technique provided better image quality than did the CSE technique, but lesion visibility was improved only with a repetition time/echo time of 2500/90; parameters of 3000/150 provided poor lesion contrast but the best myelographic effect and overall image quality. CSE images were degraded by prominent image noise; FLAIR-FSE images showed poor lesion contrast and strong cerebrospinal fluid pulsation artifacts., Conclusions: The STIR-FSE sequence is the best choice for assessment of spinal multiple sclerosis plaques. For T2-weighted FSE sequences, shorter echo times are advantageous for spinal cord imaging, long echo times are superior for extramedullary and extradural disease. FLAIR-FSE sequences do not contribute much to spinal imaging for multiple sclerosis detection.

A case of cerebral Whipple disease is reported. MR findings of the brain are discussed in relation to neuropathologic lesions reported previously. Repeated MR investigations may serve as a valuable tool to evaluate long-term efficacy of treatment in cerebral Whipple disease.

Using exploratory factor analysis, we prospectively investigated neuropsychiatric symptoms and structural brain lesions of 47 patients with proven Wilson's disease and identified three subgroups. The first subgroup clinically exhibited bradykinesia, rigidity, cognitive impairment, and an organic mood syndrome and by MRI showed a dilatation of the third ventricle. The second subgroup was characterized by ataxia, tremor, reduced functional capacity, and focal thalamic lesions. The third subgroup showed dyskinesia, dysarthria, an organic personality syndrome, and focal lesions in the putamen and in the pallidum.

Strategies proposed for the treatment of multiple sclerosis are numerous and sometimes contradictory. This review summarizes the most recent studies on the treatment of multiple sclerosis. Possibilities of influencing progression of the disease and the degree of disability suffered by patients are discussed. The treatment of acute relapses with high-dose intravenous glucocorticoids is now widely accepted because it has been shown that the duration of the relapse is reduced. Interval therapy between relapses and treatment of the chronic progressive variant of multiple sclerosis are still under debate. Immunosuppression, in particular with azathioprine, appears to have a positive effect on the long-term outcome. Whether other regimens, e.g., treatment with recombinant lymphokines, have a therapeutic effect, is difficult to assess at present since these substances have either never been tested in controlled double blind studies or the results of these studies are not yet available.

This retrospective investigation of neurological deficits in 95 consecutive patients (77 men, mean age 35 years; 18 women, mean age 28 years) infected by the human immunodeficiency virus showed that 61% of the female and 47% of the male patients exhibited neurological deficits. In 18% of the total population neurological deficits were the initial sign of acquired immunodeficiency. In addition, we found that a history of headaches and the clinical finding of mental impairment as well as internistic symptoms were significantly correlated with neurological deficits. Patients suffering from cerebral toxoplasmosis developed mental impairment significantly more often than patients with central nervous symptoms of other etiogenesis. Furthermore, it was found that HIV-infected women manifested peripheral neuropathies more often than HIV-infected men. The overall mortality rate over the investigation period of 30 months was 28%. The results of our retrospective investigation indicate that HIV-infected patients have a high risk of developing lesions of the central and peripheral nervous system during the course of the disease. Various reasons might be responsible for these findings: neurotropy and metamorphosis of the human immunodeficiency virus, opportunistic infections and tumors, vitamin deficiencies, and a variety of diseases prior to HIV-infection.